Origin & History: Found in Rhode Island Red flock. Prahlad,
KV et al. 1979 J Exp Zool 209:427-434; received from Bitgood in late 1980's.
Breed: White Leghorn background
Symbol: ll
Characteristics: Autosomal recessive, embryonic lethal
Description: Homozygotes do not develop wings or legs and usually have short upper beaks.
No image available
Additional information: Outgrowth of limb buds is initiated at
HH stage 17/18 in limbless (ll) embryos, but the apical ectodermal ridge
(AER) doesn't form at stage 18 and mutant embryos are readily identifiable
at stage 19/20. Thus limb bud initiation does not require an AER but without
it limb outgrowth ceases by stage 20/21. Limb bud mesoderm shows massive
necrosis by stage 22: buds degenerate and disappear by stage 24. The defect
is localized in the ectoderm. (Limb Development and Regeneration,
pp 33-43 1983: Development 104:361-367, 1988)
As in the case of normal limb buds deprived of their AER, explanted
ll limb buds can undergo proliferation and directed outgrowth in the presence
of exogenous FGF-2 or FGF-4. IGF-1 or insulin is more effective; in their
presence, the thin apical ectoderm of mutant limb buds is induced to form
thickened AER- like structures that can express high levels of Msx-2,
a marker for AER function. (Development 122:1323-1330, 1996)
Other gene products also stimulate enhanced outgrowth of ll limb buds
and expression of appropriate genes under various experimental conditions:
(Dev
Biol 202:43-55, 1998): TGF-alpha or EGF supplemented serum-free defined
medium - Msx2, Bmp-2, Wnt7a but not Fgf-8,
Fgf-4,
Bmp-4 or Shh
Expression
of genes associated with initiation of limb bud outgrowth has been compared
in ll and normal embryos for the following:
(Development
113:1487-1493, 1996): Ghox-7, Ghox-8
(Growth
Hormone & IGF Res 11:346-363, 2001): IGF-1, IGFBP2
(Development
122:2319-2330, 1996): Fgf-2, Fgf-4, Fgf-8, Bmp-2,
Bmp-4,
Hoxd-11, Hoxd-12, Hoxd-13, Shh,
Wnt7a,
En-1, C-Lmx1
(Dev
Biol 179:339-346, 1996): Fgf-4, Bmp-2, Bmp-4 Bmp-7,
TCF-1,
Msx-2, CEK-3, Hoxd-11, Hoxd-12,
Hoxd-13
(Development
122:3851-3861, 1996): Fgf4, Fgf8, Shh, Hoxd-11,
Hoxd-13,
Wnt7a, Lmx1, En1
(Dev
Biol 184:343-350, 1997): syndecan-3
(Dev
Biol 202:43-55, 1998): TGF-alpha, EGF, c-erb B
(Dev
Genet 25:331-338, 1999): Fgf-10, FGFR2b, Fgf-8, FGFR2c
(Develop.
Growth Differ. 44:315-325, 2002): Wnt3a, Frizzled-1, Frizzled-7,
Frizzled-3,
Frizzled-6, Lef-1, Tcf-1, Axin,
B-catenin